The aim of this proposal is to determine the role of granulocyte aggregation in the pathogenesis of pulmonary dysfunction and bronchial hyperreactivity in a spontaneously occurring model of reversible airway obstruction in the pony. This model of lung disease is unique because equids are the only domestic animals which spontaneously develop recurrent airway obstruction, similar to asthma in persons and because the condition is characterized by both pulmonary granulocyte aggregation and airway hyperreactivity. The specific objectives of this proposal are: 1. To correlate pulmonary function, airway reactivity and granulocyte numbers in ponies with recurrent bronchial obstruction during remission and during attacks of bronchospasm. 2. To determine the effect of granulocyte depletion on pulmonary function, airway reactivity and pulmonary granulocyte numbers in ponies with recurrent bronchial obstruction during remission and following exposure to hay dust. Dynamic compliance, pulmonary resistance, forced oscillating conductance, functional residual capacity, blood gas tensions and alveolar arterial oxygen differences will be measured in conscious ponies as indicators of large and small airway caliber while histamine dose-response curves will be generated to assess airway reactivity. Open lung biopsies and quantitative morphology will be used to determine granulocyte concentrations in airways, interstitium and pulmonary vasculature. If granulocytes prove to be important in the pathogenesis of derangements in airway function, our long term goal is to investigate the mechanisms whereby granulocytes produce pulmonary dysfunction.